Beta-interferon is a fibroblast-derived cytokine that exhibits antiviral, antiproliferative and immunomodulatory effects on many cell types. Recombinant human beta-interferon has proven effective in treating Multiple Sclerosis and had worldwide sales of $850 million during 1998. We propose to create modified beta-interferon proteins that can be administered less frequently, but with greater efficacy, than existing beta-interferon products. During Phase I we will identify sites in beta- interferon that can be modified without affecting the protein's in vitro bioactivity. During Phase II, we will develop manufacturing processes to produce sufficient quantities of the modified beta-interferon proteins for testing in animal disease models. The improved characteristics of the novel beta-interferon proteins should reduce the amount of beta- interferon required per patient, enhance efficacy, reduce toxicity, improve patient compliance and quality of life and result in considerable cost savings to patients and healthcare providers. Beta- interferon is a member of a large family of structurally related growth factors and cytokines. Information gained from these studies will aid in creating long-acting versions of other members of this gene family for use in treating cancer, infectious disease and hematopoietic disorders. PROPOSED COMMERCIAL APPLICATIONS: Recombinant human beta-interferon is used to treat Multiple Sclerosis and had worldwide sales of $850 million in 1998. The modified beta- interferon proteins under development will require less frequent dosing than existing beta-interferon products, resulting in significant cost savings to patients and healthcare providers. Additional expected benefits include improved drug efficacy and reduced toxicity, which will significantly enhance patient quality of life.